The effect of simvastatin treatment on proliferation and differentiation of neural stem cells after traumatic brain injury

Xie, Chuncheng; Cong, Damin; Wang, Xiujuan; Wang, Yuehua; Liang, Hongsheng; Zhang, Xiangtong; Huang, Qi

doi:10.1016/j.brainres.2014.03.021

Cited by 33 publications

(17 citation statements)

References 25 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On days 1, 3, 7, 14, 21, and 28 after TBI, a modified neurologic severity score (mNSS) (Xie et al 2015) was used to evaluate changes in neurologic functions in a blind manner. This score measures motor, sensory, reflex, and balance of the animal with the scale from 0 to 18.…”

Section: Modified Neurologic Severity Scorementioning

confidence: 99%

Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury

Dong

Ren

et al. 2015

Cell Mol Neurobiol

View full text Add to dashboard Cite

Traumatic brain injury (TBI) remains a significant clinical problem and contributes to one-third of all injury-related deaths. Activated microglia-mediated inflammatory response is a distinct characteristic underlying pathophysiology of TBI. Here, we evaluated the effect and possible mechanisms of the selective Sigma-1 receptor agonist 2-(4-morpholinethyl)-1-phenylcyclohexanecarboxylate (PRE-084) in mice TBI model. A single intraperitoneal injection 10 μg/g PRE-084, given 15 min after TBI significantly reduced lesion volume, lessened brain edema, attenuated modified neurological severity score, increased the latency time in wire hang test, and accelerated body weight recovery. Moreover, immunohistochemical analysis with Iba1 staining showed that PRE-084 lessened microglia activation. Meanwhile, PRE-084 reduced nitrosative and oxidative stress to proteins. Thus, Sigma-1 receptors play a major role in inflammatory response after TBI and may serve as useful target for TBI treatment in the future.

show abstract

Section: Modified Neurologic Severity Scorementioning

confidence: 99%

Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury

Dong

Ren

et al. 2015

Cell Mol Neurobiol

View full text Add to dashboard Cite

show abstract

“…Besides cholesterol-lowering effects, simvastatin, a HMG-CoA reductase inhibitor, is known as its neuroprotection in several brain injury models such as brain ischemia, traumatic brain injury, experimental intracerebral hemorrhage, and subarachnoid hemorrhage [19][20][21][22][23] and it has no significant toxicity effects in neonatal rats [24,25]. Its therapeutic effect might be mediated by reducing vasospasm, oxidative stress, inflammation and apoptosis, promoting angiogensis and neurogenesis, restoring endothelial function and activating phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3beta (GSK-3β) signaling pathway [23,26].…”

Section: Introductionmentioning

confidence: 99%

Simvastatin Attenuates Neurogenetic Damage and Improves Neurocongnitive Deficits Induced by Isoflurane in Neonatal Rats

Wang¹,

Lu²,

Wang³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Isoflurane inhibited neurogenesis and induced subsequent neurocognitive deficits in developing brain. Simvastatin exerts neuroprotection in a wide range of brain injury models. In the present study, we investigated whether simvastatin could attenuate neurogenetic inhibition and cognitive deficits induced by isoflurane exposure in neonatal rats. Methods: Sprague-Dawley rats at postnatal day (PND) 7 and neural stem cells (NSCs) were treated with either gas mixture, isoflurane, or simvastatin 60 min prior to isoflurane exposure, respectively. The rats were decapitated at PND 8 and PND 10 for detection of neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of the hippocampus by immunostaining. NSC proliferation, viability and apoptosis were assessed by immunohistochemistry, CCK-8 and TUNEL, respectively. The protein expressions of caspase-3, p-Akt and p-GSK-3β both in vivo and vitro were assessed by western blotting. Cognitive functions were assessed by Morris Water Maze test and context fear conditioning test at the adult. Results: Isoflurane exposure inhibited neurogenesis in the SVZ and SGZ, decreased NSC proliferation and viability, promoted NSC apoptosis and led to late cognitive deficits. Furthermore, isoflurane increased caspase-3 expression and decreased protein expressions of p-Akt and p-GSK-3β both in vivo and in vitro. Pretreatment with simvastatin attenuated isoflurane-elicited changes in NSCs and cognitive function. Co-treatment with LY294002 reversed the effect of simvastatin on NSCs in vitro. Conclusion: We for the first time showed that simvastatin, by upregulating Akt/GSK-3β signaling pathway, alleviated isoflurane-induced neurogenetic damage and neurocognitive deficits in developing rat brain.

show abstract

“…Statins, a class of hydroxymethylglutaryl-coenzyme A reductase inhibitors, are used to treat hyperlipidemia in clinic, and have shown beneficial effects for neurological disorders including TBI (Peng et al, 2014; Béziaud et al, 2011). Oral administration of synthetically derived statins, simvastatin or atorvastatin, to rats at a dose of 1mg/kg starting at day 1 following CCI injury significantly increases BrdU-labeled newly proliferated cells and BrdU/NeuN co-labeled new neurons in the DG, and improves functional recovery of the injured animals, and the effect is particularly significant with simvastatin treatment (Lu et al, 2007; Xie et al, 2014). …”

Section: Existing Fda Approved Drugsmentioning

confidence: 99%

Strategies targeting endogenous neurogenic cell response to improve recovery following traumatic brain injury

Patel

Sun

2016

Brain Research

View full text Add to dashboard Cite

Traumatic brain injury (TBI) affects over 1.7 million people in the United States alone and poses many clinical challenges due to the variability of the injuries and complexity of biochemical mechanisms involved. Thus far, there is still no effective therapy for TBI. Failure of preventative therapeutic strategies has led studies focusing on regenerative approaches. Recent studies have shown evidence that mature brains harbors multipotent neural stem cells capable of becoming mature neurons in the neurogenic regions. Following brain insults including TBI, the injured brain has increased level of neurogenic response in the subventricular zone and dentate gyrus of the hippocampus and this endogenous response is associated with cognitive function following injury. In this review, we highlight recent development and strategies aimed at targeting this endogenous cell response to enhance post-TBI functional recovery.

show abstract

The effect of simvastatin treatment on proliferation and differentiation of neural stem cells after traumatic brain injury

Cited by 33 publications

References 25 publications

Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury

Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury

Simvastatin Attenuates Neurogenetic Damage and Improves Neurocongnitive Deficits Induced by Isoflurane in Neonatal Rats

Strategies targeting endogenous neurogenic cell response to improve recovery following traumatic brain injury

Contact Info

Product

Resources

About